Cardiac output (pulmonary blood flow) is the rate at which blood is pumped by the heart to the body. Along with the blood pressure, it fundamentally reflects the degree of cardiovascular stability and the adequacy of perfusion of vital organs. Knowledge of the cardiac output will not itself provide a diagnosis of a patient's condition, but can provide information useful in making a diagnosis. Monitoring cardiac output is most important where cardiovascular instability is threatened, such as during major surgery and in critically ill patients. In these situations “moment to moment” or continuous monitoring is most desirable, since sudden fluctuations and rapid deterioration can occur, for instance, where sudden blood loss complicates an operation.
Continuous monitoring of cardiac output is still not performed routinely during anaesthesia and critical care due to the absence of a convenient, safe, non-invasive and accurate method. The established techniques for measuring cardiac output, such as pulmonary thermodilution via a pulmonary artery catheter, are invasive and associated with occasional but serious complications, such as pulmonary artery rupture, and/or are time consuming and heavily operator dependent, as in the case of Doppler echocardiography. Other indicator dilution techniques are available, but are invasive and poorly adapted to routine clinical monitoring requirements. Improvements in this field are taking place, such as the development of pulse contour techniques, transpulmonary thermodilution, and improved thoracic bioimpedance devices, but these all have limitations, such as poor accuracy under clinical conditions, the need for repeated calibration, invasive central or peripheral cannulation, and/or are simply unsuitable for patients during surgery and critical care who are intubated or ventilated.
Techniques based on pulmonary gas exchange measurement are among the oldest methods used for cardiac output measurement, and are attractive because of their potentially non-invasive nature. Recent refinements have produced systems or devices based on inert gas uptake (Innocor, Innovision, Denmark), partial CO2 rebreathing (NICO, Respironics, USA) and differential lung ventilation via a double lumen endobronchial tube (the throughflow method). (Gabrielsen et al 2002, Capek and Roy 1988, Robinson et al 2003). However, none of these alternatives allows truly continuous and non-invasive cardiac output monitoring. It follows that it would be useful to provide an automated, non-invasive, continuous measurement method and system suitable for routine use in patients undergoing general anaesthesia or in intensive care.
Non-shunt (“effective”) pulmonary capillary blood flow {dot over (Q)}c is that part of the total pulmonary blood flow (cardiac output, {dot over (Q)}t) which engages in gas exchange with an inspired gas mixture in the lung.
The Fick equation, based on the principle of conservation of mass, when applied to elimination of carbon dioxide (CO2) by the lungs, states that{dot over (Q)}t(CaCO2−C vCO2)={dot over (V)}CO2  Equation (1)where {dot over (V)}CO2 is the rate of uptake or elimination of CO2 by the lungs, and C vCO2 and CaCO2 respectively are the (dimensionless) contents of CO2 in mixed venous blood and arterial blood.{dot over (Q)}c can be related to measured {dot over (V)}CO2 by a variation of the Fick equation:
                                          Q            .                    ⁢          c                =                                                            V                .                                            CO                2                                                    (                                                Cc                                      CO                    2                                    ′                                -                                  C                  ⁢                                                            v                      _                                                              CO                      2                                                                                  )                                .                                    Equation        ⁢                                  ⁢                  (          2          )                    where Cc′CO2 and C vCO2 are the fractional contents of CO2 in pulmonary end-capillary and mixed venous blood, respectively. Since the pulmonary end-capillary blood and alveolar gas can be considered to be in equilibrium with one another, Cc′CO2 can be related to the content of CO2 in the alveolar gas mixture if the solubility of CO2 in blood is known, so that
                                          Q            .                    ⁢          c                =                                            V              .                                      CO              2                                            (                                                            S                                      CO                    2                                                  ·                                                      P                                          A                                              CO                        2                                                                                                  P                    B                                                              -                              C                ⁢                                                      v                    _                                                        CO                    2                                                                        )                                              Equation        ⁢                                  ⁢                  (          3          )                    where PACO2 is the alveolar partial pressure of CO2, and PB is the atmospheric pressure corrected for the presence of water vapour at body temperature (47 mmHg at 37° C.). SCO2 is the blood-gas partition coefficient of CO2, a constant representing the solubility of CO2 in blood under the conditions present in the patient at that time.
To permit non-invasive measurement, measured partial pressure of CO2 in end-tidal gas (PE′CO2) is used as an approximation of PACO2 so that Equation (3) can be rewritten as:
                                          Q            .                    ⁢          c                =                                            V              .                                      CO              2                                            (                                                            S                                      CO                    2                                                  ·                                                      P                                          E                                              CO                        2                                            ′                                                                            P                    B                                                              -                              C                ⁢                                                      v                    _                                                        CO                    2                                                                        )                                              Equation        ⁢                                  ⁢                  (          4          )                    {dot over (Q)}c can be determined non-invasively by application of the differential Fick principle (Capek and Roy, 1988). This combines two simultaneous versions of Equation (4) where {dot over (Q)}c and C vCO2 are assumed to be constant, as follows:
                                          Q            .                    ⁢          c                =                                                            V                .                                            CO                                  2                  ⁢                  i                                                      -                                          V                .                                            CO                                  2                  ⁢                  j                                                                                                        S                                  CO                  2                                                            P                B                                      ·                          (                                                P                                      E                                          CO                                              2                        ⁢                        i                                                              ′                                                  -                                  P                                      E                                          CO                                              2                        ⁢                        j                                                              ′                                                              )                                                          Equation        ⁢                                  ⁢                  (          5          )                    
The variables in this equation are measured at two points in time (i and j), before and after inducing a change in the alveolar minute ventilation, which alters both {dot over (V)}CO2 and PE′CO2 acutely. This can be achieved by a number of means. The first method used in the past is to make a stepwise change in the respiratory rate (Gedeon et al 1980). An alternative method, referred to as partial CO2 rebreathing, is to introduce a change in the serial deadspace, while holding tidal volume constant, thereby effectively reducing the alveolar ventilation (Capek and Roy, 1988). This is the technique used by the NICO device (Respironics, USA). This approach obviates the need to know the mixed venous CO2 content (C vCO2), which could otherwise only be directly measured by invasive mixed venous blood sampling via a pulmonary artery catheter. {dot over (Q)}c requires correction using an estimate of pulmonary shunt fraction ({dot over (Q)}s/{dot over (Q)}t). This estimate can be obtained by a number of means, including non-invasively (Peyton et al 2004). This then permits the determination of total pulmonary blood flow (cardiac output, {dot over (Q)}t), as follows:
                                          Q            .                    ⁢          t                =                                            Q              .                        ⁢            c                                1            -                                                            Q                  .                                ⁢                s                                                              Q                  .                                ⁢                t                                                                        Equation        ⁢                                  ⁢                  (          6          )                    
The acute change in {dot over (V)}CO2 and PE′CO2 rapidly levels out as washin or washout of CO2 from alveolar gas and lung tissue stores briefly approaches a new steady state level (Gedeon et al 1980, Capek and Roy, 1988). However, the change in alveolar ventilation begins to alter the content of CO2 in the mixed venous blood, Importantly, stability in both C vCO2 and {dot over (Q)}c is required for equation (6) to be accurate, and the measurement cannot be repeated more frequently than once every 3-4 minutes to allow C vCO2 to stabilise prior to the next measurement. For this reason it has not been previously possible to provide accurate continuous (breath-by-breath) monitoring of cardiac output.
Orr et al (U.S. Pat. No. 6,217,524 B1) have described an approach to the provision of continuous (breath to breath) monitoring of cardiac output, by the ongoing measurement of {dot over (V)}CO2 with each breath, following an initial baseline measurement of cardiac output and {dot over (V)}CO2. Their approach makes the assumption, based on the well-known fact that CO2 stores in the body are very large, that the arterio-venous CO2 content difference (CaCO2−C vCO2) will remain constant for some time following a change in cardiac output. From this assumption, it follows that, if {dot over (Q)}t at a breath i ({dot over (Q)}ti) changes on a subsequent breath k to {dot over (Q)}tk, then {dot over (Q)}tk can be derived from two simultaneous versions of equation (1), in which the arterio-venous CO2 content difference (CaCO2−C vCO2) cancels out, giving{dot over (Q)}tk=F·{dot over (V)}CO2k  Equation (7a)where {dot over (V)}CO2k is {dot over (V)}CO2 at breath k, and F is a scaling factor given by
                    F        =                                            Q              .                        ⁢                          t              i                                                          V              .                                      CO                              2                ⁢                i                                                                        Equation        ⁢                                  ⁢                  (                      7            ⁢            b                    )                    where {dot over (V)}CO2i is {dot over (V)}CO2 measured at breath i. This method determines an estimate of cardiac output on a breath-by-breath basis from a previous measurement of CO2 elimination by the lungs and a previous measurement of cardiac output, such as might be obtained from equation (5) above.
However, experimental testing of the Orr et al method by the inventor has found it to be unacceptably inaccurate. Continuous breath-by-breath estimations of cardiac output made using the Orr method were compared on a breath by breath basis with simultaneous measurements made by a “gold standard” in vivo measurement device, an indwelling ultrasonic flow probe placed on the ascending aorta or pulmonary artery in six ventilated sheep ranging in weight from 35-45 kg. The sheep were anaesthetised with isoflurane in oxygen-air, and their cardiac output was manipulated using a dobutamine infusion alternating with esmolol boluses. {dot over (V)}CO2 was measured at the mouth with each breath using a calibrated measurement system incorporating a pneumotachograph and sidestream rapid gas analyser. A single initial calibration cardiac output was measured by introducing a step change in tidal volume for 30 seconds and applying equation (5). Cardiac output was then followed breath-by-breath for up to 100 minutes. The results are shown in FIGS. 7 and 9.
Overall mean bias for {dot over (Q)}t (Orr et al—flow probe) was −0.34 L/min [95% confidence limits: ±0.04 L/min]. The standard deviation of the difference was 1.16 L/min, giving upper and lower limits of agreement of +1.9 and −2.6 L/min Intraclass correlation coefficients (ICC) over successive 5 minute intervals were 0.65 for agreement in {dot over (Q)}t, and 0.55 for agreement in changes in {dot over (Q)}t. From this it can be determined that only approximately 30-40% of the actual variation in cardiac output measured by the flow probe was reflected in the corresponding changes estimated by the method of Orr et al. This level of agreement with the gold standard was not improved by nominating the {dot over (Q)}t measured by the flow probe at the initial calibration point as {dot over (Q)}ti.
The method described by Orr et al produces an overdamped or “flat” response to real changes in {dot over (Q)}t. The origins of this flat responsiveness lie in the assumption underlying the method of Orr et al that the arterio-venous CO2 content difference is unaffected in the short term by changes in {dot over (Q)}t. This assumption implies a simple linear relationship between changes in {dot over (Q)}t and changes in {dot over (V)}CO2, which is not borne out by the experimental data shown in FIG. 7.
The consequence of Orr et al's assumption is a tendency to “normalise” the estimated cardiac output toward the initial baseline measurement, despite significant actual changes in {dot over (Q)}t. The clinical consequences of this are potentially serious, where the magnitude of a sudden deterioration in a patient's condition during anaesthesia for surgery, or in critical care, is underestimated, potentially resulting in an inadequate response by treating clinicians.
It is desired, therefore, to provide a method and system for monitoring cardiac output of a subject that alleviate one or more difficulties of the prior art, or at least to provide a useful alternative.